Aging: past, present and future
Aging: past, present and future
Mikhail V. Blagosklonny
In his Foundation series, published in the 1950’s, Isaac
Asimov imagined Civilization capable of colonizing the
entire Universe. This feat is unlikely to occur.
Strikingly, Asimov referred to a 70-old man as an old
individual who is unlikely to live much longer. Thus, in
literature’s most daring fantasy, the pace of aging could
not be slowed. Yet, given the present pace of discovery
in the aging field, this feat might become a reality
within our life time, with science surpassing science
fiction.
PAST
Once August Weismann had divided life into a
perishable soma and immortal germ line, the soma
began to be viewed as disposable. As Weismann wrote
in 1889, “the perishable and vulnerable nature of the
soma was the reason why nature made no effort to
endow this part of the individual with a life of unlimited
length” (see [1]). Weismann speculated that somatic
mortality might give the individual benefits early in life,
such as “a better performance of their special
physiological tasks” … or “an additional material and
energy available for the reproductive cells”. This quote
implies two hypotheses. Each of them initiated a
separate direction of thought in gerontology. First,
mortality can result from benefits at young ages (e.g.,
better performance). This idea is the root of the
antagonistic pleiotropy theory later developed by
Medawar (1952) [2] and Williams (1957) [3]. Second,
mortality can result from allocation of limited resources
for reproduction. This is the root of the allocation of
resources or disposable soma theory developed by
Kirkwood [4]. The allocation hypothesis predict that the
fewer the resources for reproduction, the shorter lifespan.
Experimental data were available to distinguish two
hypotheses as early as 1917. It was shown that caloric
restriction (CR) – a reduction in food intake without
malnutrition -- extends life span and prevents agerelated infertility in rodents [5]. These data were
initially forgotten, but have now been reproduced
numerous times. In 1930’s, McCay and his colleagues
also found that CR prolongs life span in rodents. The
significance of CR is fully appreciated only now,
knowing that nutrients modulate cellular signal
transduction pathways that include AMPK, Sirtuins and
TOR. But for a long time the effect of CR on longevity
remained just a phenomenon, albeit an important one.
Aging remained an unsolved mystery.
In 1950’s, aging began to be understood from an
evolutionary perspective. Because organisms tend to
die from external causes in the wild, the probability of
survival to old age is low. Therefore, the force of
natural selection weakens with age. Natural selection,
which is strong early in life, can favor antagonistically
pleiotropic genes (AP genes), genes that provide
benefits early in life but are harmful later. By 1957, it
was generally accepted that there were genes that are
beneficial early in life, but cause aging phenotypes at
older ages. This idea predicts that the inactivation of
some genes will extend life span, but at the cost of
development or reproduction. The identity of such
genes remained enigmatic for two reasons. First, there
were no technologies to screen for such genes at that
time. Second, it was expected that these genes must
differ among species. For example, in mammals there
might be genes responsible for rapid calcification of
bones that lead to late-life calcification of atherosclerotic plaques (an example suggested by Williams).
Nematodes such as Caenorhabditis elegans do not have
bones or a circulatory system that is susceptible to
atherosclerosis. So, aging of C. elegans and other
simple organisms was expected to be irrelevant to
human aging. Because C. elegans has a short (~3
weeks) life span and is more suitable for genetic screens
than monkeys, or, needless to say, humans,
antagonistically pleiotropic genes remained hypothetical.
Instead, research efforts were focused on obtaining
evidence for the allocation of resources hypothesis.
Aging was assumed to result from the random
accumulation of damage, resulting in chaos and an
increase of entropy that could not be regulated or
prevented. In 2006, some investigators declared that the
problem of aging had been solved [6, 7]. This view
declared that aging is just deterioration and functional
decline due to an accumulation of random molecular
damage from myriad causes, and refractory to
substantive intervention [6, 7].
But what about antagonistically pleiotropic genes
predicted in 1950’s? It was pointed out that “one of the
problems with this view, though, is that there are, in
fact, very few clear-cut examples of candidate
pleiotropic genes other than p53” [4]. https://www.aging-us.com/issue/v1i1
When general population speak of modern medicine, accuracy plays one of the most significant roles and people’s lives are directly dependent on it. Hereby, any researches pertaining to medicine are necessary to comply with the highest standards. The issue today is that any recommendations of researches can be shared online and used as a reference without being thoroughly verified and validated. Mikhail (Misha) Blagosklonny of Oncotarget clearly understood this problem and decided to develop an alternative solution. That’s how a weekly oncology-focused research journal named “Oncotarget” has been established back in 2010. The main principle of this journal is based on Altmetric scores that are used as a quality indicator. That allows both readers and authors to verify publications with Altmetric Article Reports that create “real-time feedback containing data summary related to a particular publication.” Oncotarget website has a full publications list with corresponding scores higher than 100 as well as reports mentioned previously. Mikhail (Misha) Blagosklonny glad to share his new approach and hopes it provides the necessary help to anyone, who has interest in oncology.
“A diagnostic autoantibody signature for primary cutaneous melanoma” has the Altmetric score of 594. This paper was released back in 2018 by Oncotarget and completed by diversified experts from Hollywood Private Hospital, Edith Cowan University, Dermatology Specialist Group, St. John of God Hospital and The University of Western Australia. The introduction of the study discusses “recent data shows that Australians are four times more likely to develop a cancer of the skin than any other type of cancer”, and shares an insight on melanoma that “is curable by surgical excision in the majority of cases, if detected at an early stage.”
The paper has got an Altmetric score of 594. Mikhail (Misha) Blagosklonny realizes that most of readers are willing to understand the very meaning of it. Based on the Altmetric website, the score relates to “how many people have been exposed to and engaged with a scholarly output.” Hence, the publication about melanoma, was used for citations in various news articles 69 times. Moreover, it was mentioned in 2 online blogs, as well as 25 Tweets on Twitter and 1 Facebook post. FOX23 of Tulsa, Oklahoma has headlined their report on July 20, 2018 as “New blood test could detect skin cancer early”, using the main content of Australia study
Another Oncotarget’s research with a top score of 476, is “Biomarkers for early diagnosis of malignant mesothelioma: Do we need another moon-shot,”. This publication has appeared in 60 news stories, 1 online blog post and 6 Twitter posts. The majority of public may have come across a short overview only, however those who visit Mikhail (Misha) Blagosklonny at Oncotarget, do receive useful scientific facts. Oncotarget is happy to have the chance to share with online viewers this highly appreciated and top-quality information, that is trustworthy and reliable.
Comments
Post a Comment